Alzheimer’s disease (AD) is a neurodegenerative disorder with increasing global prevalence and accounts for over half of all dementia cases. Early diagnosis is paramount for not only the management of the disease, but also for the development of new AD treatments. The current golden standard for diagnosis is performed by positron emission tomography (PET) scans with the tracer [¹¹C]Pittsburg Compound B ([¹¹C]PiB), which targets amyloid beta protein (Aβ) that builds up as plaques in the brain of AD patients. The increasing demand for AD diagnostics is in turn expected to drive an increase in [¹¹C]PiB-PET scans and the setup of new [¹¹C]PiB production lines at PET centers globally. Here, we present the [¹¹C]PiB production setups, experiences, and use from four Danish PET facilities and discuss the challenges and potential pitfalls of [¹¹C]PiB production. We report on the [¹¹C]PiB production performed with the 6-OH-BTA-0 precursor dissolved in either dry acetone or 2-butanone and by using either [¹¹C]CO₂ or [¹¹C]CH₄ as ¹¹C- precursors on three different commercial synthesis modules: TracerLab FX C Pro, ScanSys, or TracerMaker. It was found that the [¹¹C]CO₂ method gives the highest radioactive yield (1.5 to 3.2 GBq vs. 0.8 ± 0.3 GBq), while the highest molar activity (98.0 ± 61.4 GBq/μmol vs. 21.2 to 95.6 GBq/μmol) was achieved using [¹¹C]CH₄. [¹¹C]PiB production with [¹¹C]CO₂ on a TracerLab FX C Pro offered the most desirable results, with the highest yield of 3.17 ± 1.20 GBq and good molar activity of 95.6 ± 44.2 GBq/μmol. Moreover, all reported methods produced [¹¹C]PiB in quantities suitable for clinical applications, thus providing a foundation for other PET facilities seeking to establish their own [¹¹C]PiB production.

Positron emission tomography (PET) using [¹¹C]choline has recently gained clinical importance for localizing autonomous adenomas in primary hyperparathyroidism (PHPT), offering superior diagnostic accuracy and sensitivity compared to conventional [^99mTc]sestamibi scintigraphy. To meet rising clinical demand using existing infrastructure, this study evaluated three key parameters to optimize the in-house [¹¹C]choline synthesis on a TracerMaker module using [¹¹C]CH₄ as the radioactive precursor, which originally yielded 3.19 ± 0.69 GBq at end of synthesis (EOS). Three critical synthesis steps were systematically evaluated: (1) cyclotron irradiation time, (2) precursor (dimethylaminoethanol, DMAE) loading volume across Sep-Pak Accell CM cartridges, and (3) purification wash volumes. Extending irradiation time from 25 to 42 min produced no significant increase in EOS yield. Increased DMAE loading volumes up to 300 µL across 1–3 serially connected 130 mg sorbent cartridges doubled the EOS yield but elevated residual DMAE levels in the final product. Increased wash volumes of ethanol and water failed to improve purification efficiency; however, substituting the multi-cartridge system with a single higher-mass sorbent cartridge (360 mg) achieved effective DMAE removal while maintaining high EOS yield (6.46 ± 0.31 GBq). These findings demonstrate a practical route for [¹¹C]choline synthesis optimization to meet the growing clinical demand for PET imaging of PHPT.

[¹¹C]Choline ([¹¹C]CHO) has reemerged as a radiopharmaceutical tracer for positron emission tomography (PET) diagnostics and optimized synthesis setups are thus needed to meet the increased demand, often on existing production lines. Originally, [¹¹C]CHO has experienced a decline in use for PET diagnostics, particularly in prostate cancer imaging due to radiopharmaceuticals with higher target specificity. However, recent studies have demonstrated superior sensitivity and diagnostic accuracy of [¹¹C]CHO for localizing autonomous adenomas in primary hyperparathyroidism (PHPT) compared to conventional ⁹⁹ᵐTc-sestamibi scintigraphy. The PET-scan is used prior to surgery, but not for the diagnosis of PHPT. The patient compliance is high due to the relatively short time in the scanner. With this renewed clinical relevance, optimization of [¹¹C]CHO synthesis is warranted, as standard production protocols typically yield only 2.5–3.0 GBq. In this study, three critical steps in the synthesis process on a TracerMaker module were systematically evaluated and optimized. (1) Extending the irradiation time from 25 to 42 minutes produced no significant increase in radiochemical yield (RCY). (2) Increasing the precursor, dimethylaminoethanol (DMAE) loading volume to 150 µL divided across two serially connected Sep-Pak Accell CM Plus Light cartridges resulted in a twofold RCY increase but also elevated residual DMAE levels in the final product. (3) Increasing washing volumes of ethanol and water did not improve purification efficiency; however, replacing the two stacked cartridges (2 × 130 mg) with a single cartridge containing a higher sorbent mass (360 mg) achieved effective DMAE removal while maintaining high RCY. These findings demonstrate a practical route for optimizing [¹¹C]CHO synthesis to meet the growing clinical demand of [¹¹C]CHO for imaging of PHPT.